We propose to purchase a Roche GS FLX Sequencing System for use by researchers at the University of Pennsylvania and the greater Philadelphia area generally. The instrument implements massively parallel pyrophosphate sequencing to generate as much as one hundred million bases of DNA sequence in a single one-day run. This exceptionally high throughput greatly accelerates standard projects involving DNA sequencing, and makes possible altogether new research strategies leveraging the very large amounts of sequence information to address new questions. A careful survey of potential usage indicates that at least 89% of the capacity will be utilized in the first year. The University of Pennsylvania is committed to making new sequencing technology available to their faculty, and so will support a technician and programmer to facilitate use of the instrument. The instrument will be housed in the University of Pennsylvania School of Medicine DNA Sequencing Core Facility, and be operated by their staff. [unreadable] [unreadable] [unreadable]